Linked Life Data

14576830

Source:http://linkedlifedata.com/resource/pubmed/id/14576830

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
48
pubmed:dateCreated
2003-10-24
pubmed:abstractText
Activating mutations of K-ras are frequent in colon tumors and aberrant crypt foci, and may play important roles in colon carcinogenesis. Here, we investigated the effects of a K-ras codon 12 mutation on inducible nitric oxide synthase (iNOS) expression. When rat intestinal epithelial cells (IEC-6) were transfected with K-rasAsp12 cDNA, the iNOS expression linked to interleukin-1beta (IL-1beta) or lipopolysaccharide (LPS) treatment was markedly increased and prolonged. In contrast, it was only very faint and transient in cells transfected with the control vector or K-rasWT. Electrophoretic mobility-shift assays demonstrated that NF-kappaB binding activity induced by IL-1beta or LPS was also increased in K-rasAsp12-transfected cells, along with the binding of CREB-1, CREM-1, ATF-1, ATF-2, and Jun D to a cAMP-responsive element (CRE)-like site and the binding of C/EBPbeta to a C/EBP-binding consensus site. Furthermore, the anchorage-independent growth of K-rasAsp12-transfected cells was markedly increased by IL-1beta or LPS treatment, and decreased by ONO-1714, an iNOS inhibitor. In addition, tumor growth in nude mice injected with K-rasAsp12-transfected cells was significantly suppressed by NOS inhibition with 50 p.p.m. ONO-1714 or 100 p.p.m. L-NG-nitroarginine methyl ester. These results suggest that an activating mutation of K-ras can markedly enhance the iNOS expression mediated by IL-1beta or LPS, through the activation of promoters on NF-kappaB, C/EBP, and CRE-like sites, and that nitric oxide contributes to the colony formation and tumor growth of K-ras-transformed cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7667-76
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:14576830-Animals, pubmed-meshheading:14576830-Aspartic Acid, pubmed-meshheading:14576830-Cell Division, pubmed-meshheading:14576830-Cell Line, pubmed-meshheading:14576830-DNA, Complementary, pubmed-meshheading:14576830-Enzyme Inhibitors, pubmed-meshheading:14576830-Gene Expression Regulation, Enzymologic, pubmed-meshheading:14576830-Genes, ras, pubmed-meshheading:14576830-Interleukin-1, pubmed-meshheading:14576830-Intestinal Mucosa, pubmed-meshheading:14576830-Lipopolysaccharides, pubmed-meshheading:14576830-Mice, pubmed-meshheading:14576830-Mice, Nude, pubmed-meshheading:14576830-Mutation, pubmed-meshheading:14576830-NF-kappa B, pubmed-meshheading:14576830-Nitric Oxide, pubmed-meshheading:14576830-Nitric Oxide Synthase, pubmed-meshheading:14576830-Nitric Oxide Synthase Type II, pubmed-meshheading:14576830-Promoter Regions, Genetic, pubmed-meshheading:14576830-Rats, pubmed-meshheading:14576830-Response Elements, pubmed-meshheading:14576830-Transfection
pubmed:year
2003
pubmed:articleTitle
Transfection of K-rasAsp12 cDNA markedly elevates IL-1beta- and lipopolysaccharide-mediated inducible nitric oxide synthase expression in rat intestinal epithelial cells.
pubmed:affiliation
Cancer Prevention Basic Research Project, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. mtakahas@gan2.ncc.go.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't